Binding of H7N9 to Avian Receptors
Credit: Rui Xu, The Scripps Research Institute
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Research over the summer has repeatedly suggested that the newly emerging H7N9 virus in China is better adapted to mammalian hosts than many other avian influenza viruses we’ve previously seen (see Science: H7N9 Transmissibility Study In Ferrets & Nature: Limited Airborne Transmission Of H7N9 Between Ferrets), giving rise to the concern that this virus might be close to sparking a pandemic.
Yet, despite these findings, only a handful of small clusters of human infection have been documented, and the vast majority of contacts of known cases never become infected.
While the virus appears more readily transmitted from birds to humans than say, the H5N1 virus . . . it has not yet shown the crucial ability to transmit efficiently from one human to another.
Viruses constantly change, of course, and no one is entirely sure what change (or more likely, what combination of changes) are needed to fully `humanize’ this virus.
Influenza viruses have an RBD - Receptor Binding Domain (the area of its genetic sequence that allows it to attach to, and infect, host cells) that – like a key slipping into a padlock -`fit’ the receptor cells commonly found in their preferential host.
Avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds, while `humanized’ flu viruses have an affinity for the alpha 2,6 receptor cells most commonly found in the human respiratory system. .
While there are some α2-3 cells deep in the lungs of humans – which may explain the high rate of pneumonia in the unlucky few who do contract avian flu - for an influenza to be truly successful in a human host, it needs to a able to bind to the α2-6 receptor cells in the upper airway.
Today, The Scripps Research Institute (TSRI) has published their analysis of the receptor binding of the H7N9 virus to both human, and avian, receptor cells. And while this virus does, indeed bind weakly to human α2-6 receptor cells, it still shows a strong preference to bind to avian α2-3 cells.
First a link to the study, then some excerpts from the press release.
Preferential Recognition of Avian-Like Receptors in Human Influenza A H7N9 Viruses
Rui Xu, Robert P. de Vries, Xueyong Zhu, Corwin M. Nycholat, Ryan McBride, Wenli Yu, James C. Paulson,Ian A. Wilson
The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu226, a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike α2-6–linked receptors and strong preference for a subset of avian-like α2-3–linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.
TSRI scientists: Emerging bird flu strain is still poorly adapted for infecting humans
LA JOLLA, CA—December 5, 2013—Avian influenza virus H7N9, which killed several dozen people in China earlier this year, has not yet acquired the changes needed to infect humans easily, according to a new study by scientists at The Scripps Research Institute (TSRI). In contrast to some initial studies that had suggested that H7N9 poses an imminent risk of a global pandemic, the new research found, based on analyses of virus samples from the Chinese outbreak, that H7N9 is still mainly adapted for infecting birds, not humans.
"Luckily, H7N9 viruses just don't yet seem well adapted for binding to human receptors," said Ian A. Wilson, the Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI.
"Because publications to date have implied that H7N9 has adapted to human receptors, we felt we should make a clear statement about this," said James C. Paulson, chair of TSRI's Department of Cell and Molecular Biology.
The Wilson and Paulson laboratories collaborated on the study, which is reported in the December 6, 2013 issue of the journal Science.
